Monkey Protein Blocks HIV

February 26, 2004

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For years, AIDS researchers have struggled with the lack of a good animal model of HIV infection. The ideal candidates, Old World monkeys such as rhesus macaques, are not susceptible to HIV, although they are vulnerable to the monkey version of the virus, known as simian immunodeficiency virus (SIV). Scientists have suspected for some time that monkeys respond to HIV by producing a factor that stops the virus in its tracks. Now they have pinpointed this natural HIV blocker.

In a paper published today in the journal Nature, Joseph Sodroski of Harvard University and his colleagues identify this factor as a protein called TRIM5-alpha. Preventing TRIM5-alpha activity in monkey cells made infection with HIV possible, the researchers report, whereas adding the protein to human cells prevented HIV from taking hold. The protein may function by inhibiting the viruss ability to shed its protective coating, which must be removed before the virus can replicate.

TRIM5-alpha stymies HIV but not SIV, which explains why monkeys can contract only one of the two viruses. "The maintenance of a strong block to HIV-1 in Old World monkeys implies a selective advantage, presumably imposed by the presence of HIV-1-like viruses during the evolution of this primate lineage," the scientists write, adding that although humans carry a version of TRIM5-alpha, it is not as effective in thwarting HIV transmission.

The teams discovery lays the foundation for many creative approaches to developing new therapies for HIV infection and AIDS, Sodroski says. One possibility is that monkey TRIM5-alpha could be delivered to HIV patients through gene therapy to rescue as-yet-uninfected cells. Alternatively, Sodroski offers, because humans make a protein that is 87 percent identical, investigators might also focus on rendering the human version of TRIM5-alpha more potent. --Alla Katsnelson

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